Research
As a type of immunotherapy, cell therapies enhance the natural abilities of immune cells, such as T cells and natural killer (NK) cells, to detect and eliminate cancer cells at a magnitude the human body could never do alone. Cancer cells can often make themselves invisible to the immune system. Therefore, to better detect cancer cells, we can genetically modify immune cells by adding certain molecules, such as a chimeric antigen receptor (CAR). Cell therapies also can be engineered to enhance their activity against target cells.
Bringing together the top minds in the field, the Institute for Cell Therapy Discovery & Innovation will lead exceptional discovery, translational and clinical research to accelerate the development of new treatments for cancer as well as autoimmune diseases, infections and other conditions. The institute aims to provide safe and effective therapies that will be available "off-the-shelf," which could improve access and lower treatment costs.
Home to the world’s largest cancer clinical trials program, MD Anderson leverages its tremendous research engine to advance new cell therapy applications safely and quickly. We draw upon expertise in immunology, cancer genomics, drug development, data science and artificial intelligence to translate scientific discoveries into impactful treatments. By gaining new insights in immunology and cell engineering, the institute will fuel the creation of breakthrough therapies that can be readily adapted to address emerging needs.
The Institute for Cell Therapy Discovery & Innovation has a patient-centered approach to research and a focus on collaboration that allows breakthroughs to be translated into tangible, real-world, clinical therapies. MD Anderson offers the clinical infrastructure needed to run studies that can impact the lives of patients, reduce their suffering and provide them with options.
Clinical Trials in Progress
The following clinical trials are collaborations initiated by the institute.
Hematological Malignancies
-
Onco-PluReceptor + Elranatamab for Relapsed or Refractory Multiple Myeloma
PI: Qaiser Bashir, M.D.
-
Phase I/II Study of CD5 CAR Engineered IL15-Transduced Cord Blood-Derived NK Cells in Conjunction with Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Hematological Malignances
Link to more information on ClinicalTrials.gov
PI: Chitra Hosing, M.D
-
Phase I/II study of CAR.70- engineered IL15-transduced cord blood-derived NK cells in conjunction with lymphodepleting chemotherapy for the management of relapse/refractory hematological malignances
Link to more information on ClinicalTrials.gov
PI: David Marin, M.D.
-
Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas
Link to more information on ClinicalTrials.gov
PI: Yago Nieto, M.D.
-
PluReceptor NK for Patients with Recurrent or Refractory B-NHL
PI: Yago Nieto, M.D.
-
Phase II Study Assessing the Effect of BK Specific CTL Lines Generated by Ex Vivo Expansion in Stem Cell Transplant Recipients with BK Infection and JC Virus Infection
Link to more information on ClinicalTrials.gov
PI: Amanda Olson, M.D.
-
Most Closely HLA Matched Allogeneic CMV Specific Cytotoxic T-Lymphocytes (CTL) to Treat CMV Infection after Hemapoietic Stem Cell Transplantation (HSCT)
Link to more information on ClinicalTrials.gov
PI: Betul Oran, M.D.
-
Phase I/II Trial of Cord blood-derived NK cells genetically engineered with NY-ESO-1 TCR/IL-15 cell receptor for relapsed/refractory multiple myeloma
Link to more information on ClinicalTrials.gov
PI: Muzaffar Qazilbash, M.D.
-
Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies
Link to more information on ClinicalTrials.gov
PI: Jeremy Ramdial, M.D.
Hematological Malignancies and Solid Tumors
Solid Tumors
-
Phase 1 Dose Escalation and Expansion Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells in Patients with Advanced Solid Tumors (TROPIKANA)
Link to more information about this trial on breast and lung cancers on ClinicalTrials.gov
PI: Ecaterina Dumbrava, M.D.
-
PRAME TCR-Engineered NK Cells in Patients with Advanced or Metastatic Solid Tumors
PI: Ecaterina Dumbrava, M.D.
-
Donor Natural Killer Cells, Cyclophosphamide, and Etoposide in Treating Children and Young Adults With Relapsed or Refractory Solid Tumors
Link to more information on ClinicalTrials.gov
PI: Demetrios Petropoulos, M.D.
Glioblastoma
-
Dual IL13Ra/EGFRv3CAR/IL21 in GBM
PI: Shiao-Pei Weathers, M.D.
-
Phase I/II Clinical Trial of Autologous CMV-Specific Cytotoxic T Cells for GBM Patients
Link to more information on ClinicalTrials.gov
PI: Shiao-Pei Weathers, M.D.
-
A Phase I clinical trial with a window-of-opportunity component of engineered NK cells containing deleted TGF-ßR2 and NR3C1 in recurrent grade 4 astrocytoma (glioblastoma)
Link to more information on ClinicalTrials.gov
PI: Shiao-Pei Weathers, M.D.
Colorectal Cancer
-
TROP2 CAR NK cells Plus cetuximab in CRC
PI: Maria Morelli, M.D.
-
A Phase 1b Study of Immunotherapy with ex vivo Pre-Activated and expanded CB-NK cells in combination with Cetuximab, in colorectal cancer patients with minimal residual disease (MRD)
Link to more information on ClinicalTrials.gov
PI: Maria Morelli, M.D.
Other Disease Indications
-
Study Assessing the Feasibility, Safety and Efficacy of Genetically Engineered Glucocorticoid Receptor Knock Out Virus Specific CTL Lines for Viral Infections in Immunosuppressed Cancer Patients
Link to more information on ClinicalTrials.gov
PI: May Daher, M.D.
-
Phase 1 Dose Escalation and Expansion Study of PRAME T Cell Receptor (TCR) Engineered NK Cells in Participants With Recurrent and/or Refractory Melanoma (PRAMETIME-Mel)
Link to more information on ClinicalTrials.gov
PI: Adi Diab, M.D.
-
Phase I/II study of CAR.70-engineered IL15-transduced cord blood-derived NK cells in conjunction with lymphodepleting chemotherapy for the management of advanced renal cell carcinoma, mesothelioma and osteosarcoma
Link to more information on ClinicalTrials.gov
PI: David Hong, M.D.
-
AD-PluReceptor plus Tafasitamab-cxix and Lymphodepleting Chemotherapy in Patients with Autoimmune Disorders
Link to more information on ClinicalTrials.gov
PI: Chitra Hosing, M.D.
-
Phase I/II study of TROP2 CAR engineered IL15-transduced cord blood-derived NK cells delivered intraperitoneally for the management of platinum resistant ovarian cancer, mesonephric-like adenocarcinoma, and pancreatic cancer
Link to more information on ClinicalTrials.gov
PI: Amir Jazaeri, M.D.
-
Phase I/Ib study of adoptive NK expressing an affinity-enhanced T-cell receptor (TCR) reactive against the NY-ESO-1
Link to more information on ClinicalTrials.gov
PI: Andrew Livingston, M.D.
-
Administration of Expanded, Most Closely HLA Matched SARS-CoV-2-Specific T Cells for the Treatment of COVID-19 in Patients with Cancer
Link to more information on ClinicalTrials.gov
PI: David Marin, M.D.
Giulio Draetta, M.D., Ph.D.
Chief Scientific Officer
MD Anderson
The institute will leverage collaborations through multidisciplinary immunotherapy research.
Selected Publications
-
Kumar B, Singh A, Basar R, Uprety N, Li Y, Fan H, Cortes AKN, Kaplan M, Acharya S, Shaim H, Xu AC, Wu M, Ensley E, Fang D, Banerjee PP, Garcia LM, Tiberti S, Lin P, Rafei H, Munir MN, Moore M, Shanley M, Mendt M, Kerbauy LN, Liu B, Biederstädt A, Gokdemir E, Ghosh S, Kundu K, Reyes-Silva F, Jiang XR, Wan X, Gilbert AL, Dede M, Mohanty V, Dou J, Zhang P, Liu E, Muniz-Feliciano L, Deyter GM, Jain AK, Rodriguez-Sevilla JJ, Colla S, Garcia-Manero G, Shpall EJ, Chen K, Abbas HA, Rai K, Rezvani K, Daher M.
ATF is a major driver of NK cell epigenetic reprogramming and dysfunction in AML.
Sci Transl Med. 2024 Sep 11;16(764):eadp0004
-
Shanley M, Daher M, Dou J, Li S, Basar R, Rafei H, Dede M, Gumin J, Pantaleόn Garcίa J, Nunez Cortes AK, He S, Jones CM, Acharya S, Fowlkes NW, Xiong D, Singh S, Shaim H, Hicks SC, Liu B, Jain A, Zaman MF, Miao Q, Li Y, Uprety N, Liu E, Muniz-Feliciano L, Deyter GM, Mohanty V, Zhang P, Evans SE, Shpall EJ, Lang FF, Chen K, Rezvani K.
Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD.
Cancer Cell. 2024 Aug 12;42(8):1450-1466.e11.
-
Acharya S, Basar R, Daher M, Rafei H, Li P, Uprety N, Ensley E, Shanley M, Kumar B, Banerjee PP, Melo Garcia L, Lin P, Mohanty V, Kim KH, Jiang X, Pan Y, Li Y, Liu B, Nunez Cortes AK, Zhang C, Fathi M, Rezvan A, Montalvo MJ, Cha SL, Reyes-Silva F, Shrestha R, Guo X, Kundu K, Biederstadt A, Muniz-Feliciano L, Deyter GM, Kaplan M, Jiang XR, Liu E, Jain A, Roszik J, Fowlkes NW, Solis Soto LM, Raso MG, Khoury JD, Lin P, Vega F, Varadarajan N, Chen K, Marin D, Shpall EJ, Rezvani K.
CD28 costimulation augments CAR signaling in NK cells via the LCK/CD3Z/ZAP70 signaling axis.
Cancer Discov . 2024 Oct 4;14(10):1879-1900.
-
Marin D, Li Y, Basar R, Rafei H, Daher M, Dou J, Mohanty V, Dede M, Nieto Y, Uprety N, Acharya S, Liu E, Wilson J, Banerjee P, Macapinlac HA, Ganesh C, Thall PF, Bassett R, Ammari M, Rao S, Cao K, Shanley M, Kaplan M, Hosing C, Kebriaei P, Nastoupil LJ, Flowers CR, Moseley SM, Lin P, Ang S, Popat UR, Qazilbash MH, Champlin RE, Chen K, Shpall EJ, Rezvani K.
Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial.
Nat Med. 2024 Mar;30(3):772-784
-
Li Y, Rezvani K, Rafei H.
Next-generation chimeric antigen receptors for T- and natural killer-cell therapies against cancer.
Immunol Rev. 2023 Nov;320(1):217-235.
-
Li L, Mohanty V, Dou J, Huang Y, Banerjee PP, Miao Q, Lohr JG, Vijaykumar T, Frede J, Knoechel B, Muniz-Feliciano L, Laskowski TJ, Liang S, Moyes JS, Nandivada V, Basar R, Kaplan M, Daher M, Liu E, Li Y, Acharya S, Lin P, Shanley M, Rafei H, Marin D, Mielke S, Champlin RE, Shpall EJ, Chen K, Rezvani K.
Loss of metabolic fitness drives tumor resistance after CAR-NK cell therapy and can be overcome by cytokine engineering.
Sci Adv. 2023 Jul 28;9(30):eadd6997